Grand Theft Auto: San Andreas takes place within the state San Andreas, which is based on sections of California and Nevada. It comprises three major fictional cities: Los Santos corresponds to real-life Los Angeles; San Fierro corresponds to real-life San Francisco; and Las Venturas and the surrounding desert correspond to real-life Las Vegas and the Nevada and Arizona desert.

The game features set co-op scenarios in a free roam mode as well as a cooperative "rampage" gameplay mode.